The purpose of the proposed study is to elaborate the sulfate-donor specificity of 3'-phosphoadenylyl sulfate (PAPS) in the sulfoconjugation of 3-beta-hydroxysteroids and estrogens as mediated by the corresponding sulfotransferase (sulfokinase). Accordingly, a series of analogs of PAPS will be prepared in which stepwise modification of the purine ring, sugar moiety and the sulfatophosphate linkage has been effected. The suitability of these analogs to function as sulfate donors will be evaluated in terms of the Km and Vmax values for each modified structure with appropriate enzyme and acceptor. A comparison of the effect of specific structural alteration on the binding and catalytic activity of the analogs is expected to provide the basis for the design of reversible and active site-directed, irreversible inhibition of sulfoconjugation of estrogens and estrogen precursors.